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Cancer Immunology, Immunotherapy

, Volume 66, Issue 3, pp 281–298 | Cite as

Rationale and evidence to combine radiation therapy and immunotherapy for cancer treatment

  • Dan Ishihara
  • Laurentiu Pop
  • Tsuguhide Takeshima
  • Puneeth Iyengar
  • Raquibul Hannan
Review

Abstract

Cancer immunotherapy exploits the immune system’s ability to differentiate between tumor target cells and host cells. Except for limited success against a few tumor types, most immunotherapies have not achieved the desired clinical efficacy until recently. The field of cancer immunotherapy has flourished with a variety of new agents for clinical use, and remarkable progress has been made in the design of effective immunotherapeutic regimens. Furthermore, the therapeutic outcome of these novel agents is enhanced when combined with conventional cancer treatment modalities including radiotherapy (RT). An increasing number of studies have demonstrated the abscopal effect, an immunologic response occurring in cancer sites distant from irradiated areas. The present work reviews studies on the combination between RT and immunotherapy to induce synergistic and abscopal effects involved in cancer immunomodulation. Further insight into the complex interactions between the immune system and cancer cells in the tumor microenvironment, and their modulation by RT, may reveal the abscopal effect as a clinically relevant and reproducible event leading to improved cancer outcome.

Keywords

Abscopal effect Tumor immunity Immunotherapy Radiotherapy 

Abbreviations

2D

Two dimensional

3D

Three dimensional

CD

Cluster of differentiation

CTL

Cytotoxic T lymphocyte

CTLA-4

Cytotoxic T-lymphocyte-associated protein 4

DC

Dendritic cell

EBRT

External beam radiation therapy

Gy

Gray

HR

Hazard ratio

ICAM

Intracellular adhesion molecule

IFN

Interferon

IGRT

Image-guided radiation therapy

IL-2

Interleukin-2

IMRT

Intensity-modulated radiation therapy

mRCC

Metastatic renal cell carcinoma

OS

Overall survival

PD-1

Programmed death 1

PD-L1

Programmed death-ligand 1

PSA

Prostate-specific antigen

RCC

Renal cell carcinoma

RT

Radiation therapy

SAbR

Stereotactic ablative radiation

TAA

Tumor-associated antigen

TCR

T cell receptor

TGF

Transforming growth factor

TIL

Tumor-infiltrating lymphocyte

Treg

Regulatory T cell

Notes

Acknowledgments

We thank Dr. Jeffrey Meyer for his contribution to the scientific content of this review and editorial assistance. We thank Dr. Damiana Chiavolini for scientific editing. This review article was not funded.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical statements

This article does not contain any studies with human participants or animals performed by any of the authors.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Dan Ishihara
    • 1
  • Laurentiu Pop
    • 2
  • Tsuguhide Takeshima
    • 1
  • Puneeth Iyengar
    • 1
  • Raquibul Hannan
    • 1
  1. 1.Department of Radiation OncologyUT Southwestern Medical CenterDallasUSA
  2. 2.Departments of Immunology and MicrobiologyUT Southwestern Medical CenterDallasUSA

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